Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Dr. Joe Mymryk

Abstract

Protein products of the Early Region 1A (E1A) gene in human adenovirus 5 (HAdV-5) are the first viral proteins expressed upon adenovirus infection. E1A disrupts many cellular physiological events by binding to and regulating an impressive number of host factors. Of particular interest is BS69, a repressor of E1A transactivation. Due to the strong interaction observed between E1A and BS69, I hypothesize that these two proteins function together to disrupt gene expression within an infected cell.

Using in silico modelling and a series of yeast two-hybrid assays, I determined that residues 112-119 of HAdV-5 E1A is the minimal interacting region for BS69. This interaction is conserved in HAdV-5, 9, and 12 from species C, D, and A. Furthermore, I found that the MYND domain of BS69 is both necessary and sufficient to interact with and inhibit E1A-mediated transactivation in a mechanism dependent on the fidelity of the PXLXP motif and the adenovirus species. Therefore, I have found that BS69 physically interacts with E1A to disrupt gene transcription in mammalian cells. Future studies will reveal the effects of the E1A-BS69 interaction on viral growth and regulation of viral and host genes.


Included in

Virology Commons

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